The proposed research will evaluate the role of regional alterations in central catecholamine (CA) metabolism and luteinizing hormone-released hormone (LHRH) activity in the process of reproductive senescence in the female rat. Utilizing a microdissection method to accurately isolate preoptic area (POA) and hypothalamic nuclei, and sensitive radio-enzymatic methods to assay norepinephrine (NE) and dopine (DA), the influence of age on NE and DA turnover in individual POA and hypothalamic nuclei will be determined. These data will be evaluated in light of a determination of the age-related alteration in LHRH activity in the same nuclei. This procedure will allow a determination of brain nuclei where both CA and LHRH deficiencies occur in aging female rats. To evaluate the influence of age on CA-mediated gonadotropin secretion, the following, well characterized CA-mediated responses will be studied in young normally cycling, middle-aged irregularly cycling and old constant estrus rats: (1) the pulsatile release of luteinizing hormone (LH) which follows ovariectomy, (2) the increase in median eminence LHRH activity and in serum LH concentration induced by progesterone treatment of estrogen-primed ovariectomized rats, and (3) the daily surge of LH secretion induced by estrogen treatment of ovariectomized rats. Further, the ability of acute and/or chronic pharmacological stimulation of central catecholaminergic neurons to improve these CA-mediated responses will be studied in detail. Thus, the proposed research will emphasize an evaluation of the following three areas of deficiency in our knowledge of reproductive senescence in the rat: (1) the regional localization of deficiencies in CA metabolism and LHRH activity, (2) the capacity of aging female rats to secrete gonadotropins in response to CA-mediated stimuli, and (3) the responsiveness of the CA-mediated gonadotropin secretory system to activation of central CA neurons. These studies will clarify the extent of the involvement of central catecholaminergic systems in reproductive aging in the female rat.